Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Regul Toxicol Pharmacol. 2010 Nov;58(2):196-207. doi: 10.1016/j.yrtph.2010.05.008. Epub 2010 May 23.
The purpose of this study was to investigate the potential toxicity of gemifloxacin by 28-day repeated oral dose in Wistar albino rats. The test article, was administered daily by gavage to male and female rats at dose levels of 0, 50, 100, 200 mg/kg/day. At the end of treatment period, 12 rats/sex/group was sacrificed, while six extra rats/sex in the vehicle control and highest dose groups sacrificed after 14 days recovery period. During the treatment and recovery periods, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, phototoxicity, hematology, serum biochemistry, synovial fluid biochemistry, electrocardiogram (ECG), gross findings, organ weights, microscopic examination of synovial fluid, and histopathology were examined. Hematological and serum biochemical investigations revealed a dose-dependent increase in the total white blood cell (WBC), total bilirubin (T-BIL), glucose (GLU), alanine aminotransferase (ALT) and significant decreases in total protein (TP) were observed in both sexes at the same dose, at the end of treatment period, but the levels returned toward normal during the recovery period. Histopathology of talar joint showed that erosion of the articular surface of that joint in both sexes at the end of treatment period at the dose level of 200 mg/kg/day. Degenerative changes in tendinocytes were observed in Achilles tendon of both sexes at the high dose level at the end of treatment period. In histopathological study shows partial effacement of liver architecture and focal ulceration in gastric mucosa at the high dose level at the end of treatment period. Based on these results, it was concluded that 28 days repeated oral dose of gemifloxacin caused increases in the liver weight, WBC count, T-BIL, glucose level, ALT, decreasing the TP, cause chronic hepatitis and acute gastritis, erosion of the articular surface of joint and histopathologic changes in Achilles tendon in rats at the dose level of 200 mg/kg/day.
本研究旨在通过 28 天重复口服剂量研究加替沙星对 Wistar 白化大鼠的潜在毒性。试验药物以 0、50、100、200mg/kg/天的剂量水平通过灌胃每日给予雄性和雌性大鼠。在治疗期末，每组处死 12 只大鼠，而在载体对照组和最高剂量组中，另外 6 只雄性和 6 只雌性大鼠在 14 天恢复期后处死。在治疗和恢复期期间，观察临床症状、死亡率、体重、食物和水消耗、眼科学、尿液分析、光毒性、血液学、血清生物化学、滑液生物化学、心电图（ECG）、大体观察、器官重量、滑液的显微镜检查和组织病理学。血液学和血清生化研究表明，在同一剂量下，雄性和雌性在治疗期末均出现总白细胞（WBC）、总胆红素（T-BIL）、葡萄糖（GLU）、丙氨酸氨基转移酶（ALT）的剂量依赖性增加，总蛋白（TP）显著降低，在恢复期内，这些水平恢复正常。距骨关节的组织病理学显示，在治疗期末，雄性和雌性在 200mg/kg/天的剂量水平下，该关节的关节表面出现侵蚀。在治疗期末，在高剂量水平下，两性的跟腱中的腱细胞发生退行性变化。在组织病理学研究中，在治疗期末高剂量水平下，肝脏结构部分消失，胃黏膜出现局灶性溃疡。基于这些结果，可以得出结论，28 天重复口服加替沙星剂量导致肝脏重量增加、白细胞计数增加、T-BIL、葡萄糖水平升高、ALT 升高、TP 降低，导致慢性肝炎和急性胃炎，关节表面侵蚀关节和跟腱的组织病理学变化在 200mg/kg/天的剂量水平下的大鼠。
